This invention relates to bioabsorbable materials such as a terpolymer of poly-(L-lactide/D-lactide/glycolide), methods of making and using such materials, and to medical devices made from such materials.
Commercially available bone fixation devices are often made of metal alloys which must be surgically removed after bone healing. The removal of such devices causes additional trauma to the patient as well as increased medical costs. Metallic devices also have moduli of elasticity which are 10-20 times higher than that of cortical bone, thus preventing the loading of the bone and possibly causing osteopenia due to stress shielding.
U.S. Pat. Nos. 4,539,981 and 4,550,449 to Tunc (the inventor of the present invention) relate to absorbable bone fixation devices made from high molecular weight polymer of L-lactide. However, such fixation devices have a relatively low rate of absorption and retain relatively high tensile strength after the bone fully heals.
U.S. Pat. No. 5,569,250 to Sarver et al. relates to a biocompatible osteosynthesis plate for securing a plurality of adjacent bone portions. It purportedly discloses, inter alia, non-reinforced lactide and glycolide copolymer (see, e.g., col. 6, lines 63 et seq.). However, such materials exhibit relatively low tensile strengths.
All documents cited herein, including the foregoing, are incorporated herein by reference in their entireties for all purposes.
It is an object of this invention to obtain an implantable medical device having relatively high strength retention during the early periods of bone healing, but with a sufficiently high absorption rate so that the material is at least substantially absorbed at the time that the bone is fully healed. Preferably the device will be contourable before use (e.g., its shape can be modified to more closely complement the shape of the bone to which it will be attached) and preferably it will provide a closer match of mechanical properties of bone as compared to known devices.
To that end, a novel material has been invented which contains poly-(L-lactide/D-lactide/glycolide) also referred to hereinafter as p-(LLA/DLA/GA). This material provides mechanical properties which are desirable for certain implantable medical devices such as bone fixation devices.
In sum, the present invention relates to material comprising poly-(L-lactide/D-lactide/glycolide), preferably comprising at least about 2 molar percent D-lactide and more preferably comprising at least about 4 molar percent D-lactide. The material may have about 2 to about 10 molar percent D-lactide and/or about 80-90 molar percent L-lactide and/or about 5-15 molar percent glycolide. Especially preferred is a material comprising about 83-87 molar percent L-lactide, about 3-7 molar percent D-lactide, and about 8-12 molar percent glycolide. The material may further comprise about 0.1-5 molar percent of a polymer formed from alpha-hydroxy-alpha-ethylbutyric acid; alpha-hydroxy-beta-methylvaleric acid; alpha-hydroxyacetic acid; alpha-hydroxybutyric acid; alpha-hydroxycaproic acid; alpha-hydroxydecanoic acid; alpha-hydroxyheptanoic acid; alpha-hydroxyisobutyric acid; alpha-hydroxyisocaproic acid; alpha-hydroxyisovaleric acid; alpha-hydroxymyristic acid; alpha-hydroxyoctanoic acid; alpha-hydroxystearic acid; alpha-hydroxyvaleric acid; beta-butyrolactone; beta-propiolactide; gamma-butyrolactone; pivalolactone; or tetramethylglycolide; or combinations thereof.
The invention also relates to a process of making a material, and the material so made, the process comprising: a) combining L-lactic acid monomer, glycolic acid monomer and at least about 2 molar percent D-lactic acid monomer to form a mixture; and b) polymerizing substantially all of the mixture. The polymerization may be preformed in the presence of a catalyst and for between 24 and 72 hours.
The invention also relates to an implantable medical device comprising poly-(L-lactide/D-lactide/glycolide). The medical device may be a bone plate, bone screw, mesh, suture anchor, tack, pin or intramedullary rod. The medical device can consist essentially of unreinforced poly-(L-lactide/D-lactide/glycolide) or reinforced poly-(L-lactide/D-lactide/glycolide).
The invention also relates to a method of using a bioabsorbable bone fixation device, the method comprising: a) providing a bioabsorbable bone fixation device comprising poly-(L-lactide/D-lactide/glycolide), the device disposed in a first shape in a free state; then b) heating the bone fixation device; and then c) applying force to the device so that the device obtains a second shape in a free state which is different than the first shape and which approaches the shape of a bone surface to which it will be attached. The heating may be preformed at between about 55xc2x0 C. to about 130xc2x0 C. for between about 2 to about 10 seconds.
The invention also relates to polymeric resin having a heat of fusion of about 0.4-10, preferably 0.5-5 J/G, and/or a molded polymeric material having a heat of fusion of about 15 to about 25 J/G, and tensile strength retention at 26 weeks of incubation of at least about 50%, and tensile strength retention at 52 weeks of incubation of at most about 25%. The polymeric material may comprise poly-(L-lactide/D-lactide/glycolide) preferably comprising at least about 2 molar percent D-lactide.
The present invention also relates to a polymeric material having tensile strength at 0 weeks of incubation of about 65-101 MPa, tensile strength at 26 weeks of incubation of about 50-75 MPa, tensile strength at 44 weeks of incubation of about 0-37 MPa, and tensile strength at 60 weeks of incubation of 0 MPa. The polymeric material may comprise poly-(L-lactide/D-lactide/glycolide) and may had a heat of fusion of about 15-25 J/G preferably about 18-21 J/G. The polymeric material may have a tensile strength at 0 weeks of incubation of about 74-92 MPa, tensile strength at 26 weeks of incubation of about 56-69 MPa, and tensile strength at 44 weeks of incubation of about 9-27 MPa.